Bifidobacterium animalis subsp. lactis F1–7 Alleviates Lipid Accumulation in Atherosclerotic Mice via Modulating Bile Acid Metabolites to Downregulate Intestinal FXR

The dysfunction of intestinal microbiota and bile acid metabolism is related to the pathogenesis of atherosclerosis. This study we explored the mechanism of Bifidobacterium animalis subsp. lactis F1–7 (Bif. animalis F1–7), improving atherosclerosis by regulating the bile acid metabolism and intestinal microbiota in the ApoE^–/– mice. The Bif. animalis F1–7 effectively reduced aortic plaque accumulation and improved the serum and liver lipid levels in atherosclerotic mice. The untargeted metabolomics revealed that Bif. animalis F1–7 reduced the glycine-conjugated bile acids and the levels of differential metabolite lithocholic acid (LCA) significantly. Downregulation of LCA decreased the intestinal levels of the farnesoid X-activated receptor (FXR) and regulated the bile acid metabolism through the FXR/FGF15/CYP7A1 pathway. Furthermore, the 16srRNA gene sequencing analysis revealed that structural changes in intestinal microbiota with an increase in the abundance of Bifidobacterium, Lactobacillus, Faecalibaculum, Desulfovibrio, and a decrease in Dubosiella, Clostridium_sensu_stricto_1, and Turicibacter following the Bif. animalis F1–7 intervention. Correlation analysis showed that the changes in intestinal microbiota mentioned above were significantly correlated with bile acid metabolism in atherosclerotic mice. In conclusion, this study sheds light on the mechanisms by which Bif. animalis F1–7 regulates atherosclerosis.